Intravenous Hemin, a potential heme oxygenase-1 activator, does not protect from post-ERCP acute pancreatitis in humans: Results of a randomized multicentric multinational placebo-controlled trial.

OBJECTIVE: Hemin, a heme oxygenase 1 activator has shown efficacy in the prevention and treatment of acute pancreatitis in mouse models. We conducted a randomized controlled trial (RCT) to assess the protective effect of Hemin administration to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients at risk. METHODS: In this multicenter, multinational, placebo-controlled, double-blind RCT, we assigned patients at risk for PEP to receive a single intravenous dose of Hemin (4 mg/kg) or placebo immediately after ERCP. Patients were considered to be at risk on the basis of validated patient- and/or procedure-related risk factors. Neither rectal NSAIDs nor pancreatic stent insertion were allowed in randomized patients. The primary outcome was the incidence of PEP. Secondary outcomes included lipase elevation, mortality, safety, and length of stay. RESULTS: A total of 282 of the 294 randomized patients had complete follow-up. Groups were similar in terms of clinical, laboratory, and technical risk factors for PEP. PEP occurred in 16 of 142 patients (11.3%) in the Hemin group and in 20 of 140 patients (14.3%) in the placebo group (p = 0.48). Incidence of severe PEP reached 0.7% and 4.3% in the Hemin and placebo groups, respectively (p = 0.07). Significant lipase elevation after ERCP did not differ between groups. Length of hospital stay, mortality and severe adverse events rates were similar between groups. CONCLUSION: We failed to detect large improvements in PEP rate among participants at risk for PEP who received IV hemin immediately after the procedure compared to placebo. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT01855841).

Intensive Enteral Nutrition Is Ineffective for Patients With Severe Alcoholic Hepatitis Treated With Corticosteroids.

BACKGROUND & AIMS: Severe alcoholic hepatitis (AH) is a life-threatening disease for which adequate oral nutritional support is recommended. We performed a randomized controlled trial to determine whether the combination of corticosteroid and intensive enteral nutrition therapy is more effective than corticosteroid therapy alone in patients with severe AH. METHODS: We enrolled 136 heavy consumers of alcohol (age, 18-75 y) with recent onset of jaundice and biopsy-proven severe AH in our study, performed at 18 hospitals in Belgium and 2 in France, from February 2010 through February 2013. Subjects were assigned randomly (1:1) to groups that received either intensive enteral nutrition plus methylprednisolone or conventional nutrition plus methylprednisolone (controls). In the intensive enteral nutrition group, enteral nutrition was given via feeding tube for 14 days. The primary end point was patient survival for 6 months. RESULTS: In an intention-to-treat analysis, we found no significant difference between groups in 6-month cumulative mortality: 44.4% of patients died in the intensive enteral nutrition group (95% confidence interval [CI], 32.2%-55.9%) and 52.1% of controls died (95% CI, 39.4%-63.4%) (P = .406). The enteral feeding tube was withdrawn prematurely from 48.5% of patients, and serious adverse events considered to be related to enteral nutrition occurred in 5 patients. Regardless of group, a greater proportion of patients with a daily calorie intake less than 21.5 kcal/kg/day died (65.8%; 95% CI, 48.8-78.4) than patients with a higher intake of calories (33.1%; 95% CI, 23.1%-43.4%) (P < .001). CONCLUSIONS: In a randomized trial of patients with severe AH treated with corticosteroids, we found that intensive enteral nutrition was difficult to implement and did not increase survival. However, low daily energy intake was associated with greater mortality, so adequate nutritional intake should be a main goal for treatment. ClinicalTrials.gov number: NCT01801332.

Pancreatic tuberculosis diagnosed by EUS: one disease, many faces.

CONTEXT: Pancreatic/para-pancreatic tuberculosis is an extremely rare clinical entity even in endemic regions. It can present as a cystic or solid pancreatic mass mimicking pancreatic malignancy. There are no specific imaging criteria and the clinical symptoms remain vague. Therefore, most cases are diagnosed after surgical exploration for presumed pancreatic neoplasia. CASE REPORT: We report five cases of pancreatic tuberculosis each time with a different clinical presentation, in an occidental country setting where the diagnosis was done by EUS guided FNA (EUS-FNA). CONCLUSION: EUS-FNA is a safe and promising technique for the diagnosis of pancreatic/para-pancreatic tuberculosis, avoiding unnecessary surgery.

Enteral nutrition with or without N-acetylcysteine in the treatment of severe acute alcoholic hepatitis: a randomized multicenter controlled trial.

BACKGROUND & AIMS: Severe acute alcoholic hepatitis is associated with a high mortality rate. Oxidative stress is involved in the pathogenesis of acute alcoholic hepatitis. Previous findings had also suggested that enteral nutritional support might increase survival in patients with severe acute alcoholic hepatitis. Therefore, the aim of the present study was to evaluate the efficacy of N-acetylcysteine in combination with adequate nutritional support in patients with severe acute alcoholic hepatitis. METHODS: Patients with biopsy-proven acute alcoholic hepatitis and mDF ≥32 were randomized to receive N-acetylcysteine intravenously or a placebo perfusion along with adequate nutritional support for 14 days. The primary endpoint was 6-month survival; secondary endpoints were biological parameter evolution and infection rate. RESULTS: Fifty-two patients were randomized in the study (28 into the N-acetylcysteine arm, 24 into the control arm), and among them, five were excluded from the analysis for protocol violation. The two groups did not differ in baseline characteristics. Survival rates at 1 and 6 months in N-acetylcysteine and control groups were 70.2 vs. 83.8% (p=0.26) and 62.4 vs. 67.1% (p=0.60), respectively. Early biological changes, documented infection rate at 1 month, and incidence of hepatorenal syndrome did not differ between the two groups. CONCLUSIONS: In this study, high doses of intravenous N-acetylcysteine therapy for 14 days conferred neither survival benefits nor early biological improvement in severe acute alcoholic hepatitis patients with adequate nutritional support. However, these results must be viewed with caution, since the study suffered from a lack of power.

Single vs repeated treatment with the intragastric balloon: a 5-year weight loss study.

BACKGROUND: Saline-filled intragastric balloons (IB) may be inserted for 6 months to promote weight loss. We aimed to assess potential benefits of repeating IB therapy. METHODS: One hundred eighteen consecutive subjects (median body mass index, 34.0 kg/m(2); interquartile range [IQR], 31.2-36.9) treated with IB were included in a prospective non-randomized multicenter study. RESULTS: Nineteen (16%) subjects had repeat IB therapy at their own request, either to prolong first treatment (n = 8) or after a IB-free interval (n = 11). Higher weight loss 3 months after first IB insertion independently predicted repeat therapy (P = 0.008). Median weight loss in subjects who had repeat therapy was lower with second vs first IB (9.0 vs 14.6 kg; 30.4% vs 49.3% excess weight [EW]; P = 0.003). Compared to subjects with single treatment (n = 99), those with repeat treatment (n = 19) had greater weight loss at first IB extraction (14.6 vs 11.0 kg; 49.3% vs 30.7% EW; P = 0.026) and 1 year later (12.0 vs 6.0 kg; 40.9% vs 20.8% EW; P = 0.008) but the difference became less than 2 kg starting at 3 years. At final follow-up (4.9 years; IQR, 3.4-6.7), the whole subject population had lost a median of 2.0 kg (IQR, -3.0 to 10.3) or 6.2% EW (IQR, -8.1 to 31.6) and identical proportions of subjects with single/repeat treatment had >or=10% baseline weight loss (26%) or bariatric surgery (32%). CONCLUSION: Higher weight loss at 3 months independently predicted repeat IB therapy; weight loss with the second IB was lower compared to first IB. Repeat treatment had no effect on proportions of subjects with >or=10% baseline weight loss or bariatric surgery at final follow-up.

EUS-guided pancreatogastrostomy and pancreatobulbostomy for the treatment of pain in patients with pancreatic ductal dilatation inaccessible for transpapillary endoscopic therapy.

BACKGROUND: EUS-guided pancreatogastrostomy (EPG) is described as an alternative to surgery for ductal decompression in symptomatic patients when endoscopic transpapillary access of the main pancreatic duct (MPD) is impossible. OBJECTIVE: To present the midterm clinical response and follow-up of a larger group of patients treated with EPG and a new transbulbar approach, EUS-guided pancreatobulbostomy (EPB). DESIGN: Retrospective case review. SETTING: Two tertiary referral centers in Brussels and Marseille. PATIENTS: From 2000 to 2004, 36 patients (51 years old; range, 14-71 years) were seen. INTERVENTION: EPG or EPB. MAIN OUTCOME MEASUREMENTS: Pain relief, technical aspects, complications, and clinical follow-up. RESULTS: Indications were chronic pancreatitis, with complete obstruction (secondary to a tight stenosis, a stone, or MPD rupture); inaccessible papilla or impossible cannulation (n = 20); anastomotic stenosis after a Whipple procedure (n = 12); complete MPD rupture after acute pancreatitis (AP); or trauma (n = 4). EPG or EPB was unsuccessful in 3 patients; 1 was lost to follow-up. Major complications occurred in 2 patients and included 1 hematoma and 1 severe AP. The median follow-up was 14.5 months (range, 4-55 months). Pain relief was complete or partial in 25 patients (69%, intention to treat). Eight patients treated had no improvement of their symptoms (4 were subsequently diagnosed with cancer). Stent dysfunction occurred in 20 patients (55%) and required a total of 29 repeat endoscopies. LIMITATIONS: Technically demanding and requires careful pretherapeutic evaluation. CONCLUSIONS: EPG or EPB appears to be an effective and relatively safe treatment for the management of pain secondary to pancreatic ductal hypertension in patients with an MPD not accessible by a transpapillary route.

Treatment for painful calcified chronic pancreatitis: extracorporeal shock wave lithotripsy versus endoscopic treatment: a randomised controlled trial.

BACKGROUND: In chronic pancreatitis, obstruction of the main pancreatic duct (MPD) may contribute to the pathogenesis of pain. Pilot studies suggest that extracorporeal shock wave lithotripsy (ESWL) alone relieves pain in calcified chronic pancreatitis. AIM: To compare ESWL alone with ESWL and endoscopic drainage of the MPD for treatment of pain in chronic pancreatitis. SUBJECTS: Patients with uncomplicated painful chronic pancreatitis and calcifications obstructing the MPD. METHODS: 55 patients were randomised to ESWL alone (n = 26) or ESWL combined with endoscopy (n = 29). RESULTS: 2 years after trial intervention, 10 (38%) and 13 (45%) patients of the ESWL alone and ESWL combined with endoscopy group, respectively, had presented pain relapse (primary outcome) (OR 0.77; 95% CI 0.23 to 2.57). In both groups, a similar decrease was seen after treatment in the MPD diameter (mean decrease 1.7 mm; 95% CI 0.9 to 2.6; p<0.001), and in the number of pain episodes/year (mean decrease, 3.7; 95% CI 2.6 to 4.9; p<0.001). Treatment costs per patient were three times higher in the ESWL combined with endoscopy group compared with the ESWL alone group (p = 0.001). The median delay between the onset of chronic pancreatitis and persistent pain relief for both groups was 1.1 year (95% CI 0.7 to 1.6), as compared with 4 years (95% CI 3 to 4) for the natural history of chronic pancreatitis in a reference cohort (p<0.001). CONCLUSIONS: ESWL is a safe and effective preferred treatment for selected patients with painful calcified chronic pancreatitis. Combining systematic endoscopy with ESWL adds to the cost of patient care, without improving the outcome of pancreatic pain.

A prospective comparative study of push and wireless-capsule enteroscopy in patients with obscure digestive bleeding.

OBJECTIVES: To prospectively compare the global and specific diagnostic yields of push and wireless videocapsule enteroscopy for small bowel lesions in patients with obscure digestive bleeding after esogastroduodenoscopy and colonoscopy. METHODS: The patients studied had unexplained chronic iron-deficient anemia or digestive blood loss after routine investigations. Small bowel investigation was performed first with the wireless-capsule (M2A, Given Imaging) and then with the push-enteroscope (Olympus SIF100). RESULTS: Twenty-one patients were included in the protocol (14 females and 7 males), whose mean age was 60 years (range: 18 to 81). All patients had iron-deficient anemia with occult bleeding (n = 16) or overt bleeding (n = 5). A digestive lesion was observed in 14 of 21 cases (66%). Lesions were: esophageal varices (n = 2), reflux esophagitis (n = 1), upper gastrointestinal tract ulcerations (n = 9), intestinal angioectasia (n = 4), ileal varices (n = 1), cecal angioectasia (n = 1) and tumor-like angioma in the jejunum (n = 1). These 19 lesions were discovered by both methods in 10 cases (52%), by push-enteroscopy only in 6 (31%) and by wireless-capsule endoscopy only in 3 (17%). The global diagnostic yield was therefore slightly but not significantly higher for push wireless-capsule enteroscopy (61 vs 52%; NS) and the specific diagnostic yield was similar (20%). Interobserver agreement on the wireless-capsule recordings reached 85% for detection of findings. CONCLUSIONS: In patients with obscure digestive bleeding, no significant difference in diagnostic yield was evidenced between push and wireless-capsule endoscopy. The main advantage of the latter method versus the former was the detection of distal lesions in the small bowel. Wireless-capsule enteroscopy is mandatory for patients with active unexplained bleeding and negative push-enteroscopy, or for defining the extension of a disease involving, for instance, the presence of angioectasia.

Binding sites for Lewis antigens are expressed by human colon cancer cells and negatively affect their migration.

In colon cancer, endothelial cell selectins can promote tumor cell attachment via interactions with sialylated Lewis antigens present at the surface of tumor cells, thereby facilitating tumor cell arrest and transmigration into the extravascular space. However, it is not known whether Lewis antigens interact with colon tumor cells and modify their migration. Our aim was to detect the presence of binding sites on human tumor cells for Lewis(a/x) antigens and their sialylated derivatives in vitro and in vivo and to analyze their influence on migration of colon cancer cells. The immunocytochemical and histochemical levels of expression of the four Lewis antigens were quantitatively determined in four human colon cancer cell lines and in in vivo nude mice xenografts. The levels of expression of specific binding sites for these sugar epitopes were determined by synthetic neoglycoconjugates. The influence of binding of these carbohydrate ligands on cancer cell migration was quantitatively evaluated by computer-assisted phase-contrast videomicroscopy performed on Matrigel culture supports either left uncoated or coated with neoglycoconjugate presenting synthetic Lewis(a), sialyl Lewis(a), Lewis(x), or sialyl Lewis(x) antigens. The influence of the calcium concentration in the culture medium on the Lewis antigen-mediated effects was checked. Human colon cancer cells expressed significant amounts of specific binding sites detected by the synthetic probes in addition to the oligosaccharide epitopes. The expression levels differed considerably between the four cell lines and between in vitro and in vivo specimens. Cell migration analysis revealed that the four Lewis antigens markedly decreased the levels of migration of the HCT-15 and LoVo cancer cells. This effect depends on the calcium concentration in the culture medium. Binding sites for Lewis epitopes are present on colon cancer cells. The functional relevance of these sites is indicated by the negative influence on cell migration of a matrix containing the oligosaccharides as ligand parts.

Management of anticoagulants before and after endoscopy.

The risk of procedure-related bleeding while taking anticoagulants needs to be weighed against the risk of thromboembolism from discontinuing these drugs. It is not necessary to adjust anticoagulation for low-risk procedures, such as upper endoscopy with biopsy, colonoscopy with biopsy or endoscopic retrograde cholangiopancreatography with stent insertion (but without sphincterotomy). Procedures that incur a high risk of bleeding include polypectomy, endoscopic sphincterotomy, laser therapy, mucosal ablation and treatment of varices. For these procedures, warfarin should be discontinued four to five days beforehand. Depending on the risk of thromboembolism, that is based on the nature of the underlying condition, the patient may require vitamin K and/or fresh frozen plasma (to ensure that coagulation parameters are within the normal range) or heparin infusions (to ensure that some degree of anticoagulation is maintained). Low molecular weight heparin is an alternative to unfractionated heparin for select cases with a high risk of thromboembolism. Warfarin therapy may generally be resumed on the night of the procedure and may be supplemented by heparin in patients with a high risk of thromboembolism. It is not necessary to discontinue acetylsalicylic acid or nonsteroidal anti-inflammatory drugs, when used in standard doses, for endoscopic procedures. There are insufficient data to make recommendations regarding newer antiplatelet drugs, such as ticlopidine or clopidogrel, but it is prudent to discontinue these medications seven to 10 days before a high-risk procedure.

Upregulation of galectins-1 and -3 in human colon cancer and their role in regulating cell migration.

To probe the potential contribution of beta-galactoside-contributing epitopes and receptor proteins (gal-1 and gal-3) to colon malignancy, we first examined the expression of galectins and binding sites in clinical specimens by lectin and immunohistochemistry. Sixty-seven colonic surgical resections were studied, including 10 normal, 10 mild dysplasias, 10 severe dysplasias and 37 cancers. gal-1 and gal-3 were expressed in variable amounts in the epithelial cells and the connective tissue of normal colon. Their expression significantly increased with the degree of dysplasia, suggesting that gal-1 and gal-3 and their binding sites are related to malignant progression, while gal-8 has been associated with suppressor activity. To study the functional aspects, the influence of these galectins on the migration of 4 human colorectal cancer cell lines (HCT-15, LoVo, DLD-1, CoLo201) was studied. In agreement with histopathologic monitoring, these tumor cells were found to produce gal-3, while only CoLo201 was positive for gal-1. Except for DLD-1 and gal-1, the lines exhibited gal-1 binding sites on the surface, prompting study by computer-assisted videomicroscopy of the effect on cell migration of the presence of galectin on the culture substrate. The level of cell migration for HCT-15, LoVo and CoLo201 cells was significantly reduced by 0.15 microg/cm(2) gal-1, and the presence of a blocking antibody at least reduced this effect. gal-3 significantly reduced cell migration in all 4 of the in vitro cell lines.